title: Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.
abstract: Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short-term cultures using good manufacturing practice-compliant reagents. This process uses CD40L-activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.
authors.affiliation: UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA.
authors.forename: A L
authors.initials: AL
authors.lastname: Putnam
authors.forename: N
authors.initials: N
authors.lastname: Safinia
authors.forename: A
authors.initials: A
authors.lastname: Medvec
authors.forename: M
authors.initials: M
authors.lastname: Laszkowska
authors.forename: M
authors.initials: M
authors.lastname: Wray
authors.forename: M A
authors.initials: MA
authors.lastname: Mintz
authors.forename: E
authors.initials: E
authors.lastname: Trotta
authors.forename: G L
authors.initials: GL
authors.lastname: Szot
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Lares
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Laing
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
authors.forename: J L
authors.initials: JL
authors.lastname: Riley
authors.forename: J A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
authors.forename: Q
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*; D023001:Transplantation Tolerance
chemical_list: D007519:Isoantigens
keywords: Cellular therapy; clinical application; regulatory T cells; tolerance induction